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Calcium carbonate poly(lactic acid-glycolic acid) composite particle and preparation and application thereof

A technology of glycolic acid and calcium carbonate, which is applied in the direction of drug combination, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problems of severe immunosuppressive microenvironment, achieve good loading efficiency, particle Uniform diameter, to achieve the effect of responsive release

Active Publication Date: 2020-11-06
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, a variety of solid tumors highly express indoleamine 2,3-dioxygenase 1 (IDO-1), which can catalyze the degradation of intratumoral tryptophan (Trp) into kynurenine (Kyn) , and the accumulation of kynurenine in the tumor will not only reduce the infiltration of Th1, CTL and other T cells into the tumor and induce their apoptosis, but also activate the immune regulatory T cells (Tregs) in the tumor, resulting in severe immunosuppression sexual microenvironment

Method used

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  • Calcium carbonate poly(lactic acid-glycolic acid) composite particle and preparation and application thereof
  • Calcium carbonate poly(lactic acid-glycolic acid) composite particle and preparation and application thereof
  • Calcium carbonate poly(lactic acid-glycolic acid) composite particle and preparation and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0038] Example 1: Preparation of calcium carbonate poly(lactic acid-glycolic acid) complex-DOX-NLG919 preparation

[0039] Dissolve NLG919 in dichloromethane solution, use N,N-diisopropylethylamine (DIPEA) as the base, add dodecyl chloride to the reaction system under ice bath conditions, and react to generate alkyl-modified NLG919. The product aNGL919 was obtained by liquid chromatography column purification.

[0040] W / O emulsion A and emulsion B were prepared by ultrasonic emulsification, and the aqueous phase of emulsion A was NaHCO 3 solution, the oil phase is a dichloromethane solution of PLGA, PLGA-PEG and aNLG919; the water phase of emulsion B is DOX dissolved in CaCl 2 solution, the oil phase is also the dichloromethane solution of PLGA, PLGA-PEG and aNLG919. Mix emulsions A and B after ultrasonic emulsification respectively, continue ultrasonication to obtain emulsion C, and finally disperse in 1% PVA aqueous solution to obtain W1 / O / W2 microemulsion system, stir ov...

Embodiment 2

[0041] Embodiment two: the property detection of calcium carbonate poly(lactic acid-glycolic acid) complex-DOX-NLG919 preparation

[0042]The calcium carbonate poly(lactic acid-glycolic acid) complex-DOX-NLG919 preparation prepared in Example 1 was qualitatively detected, and transmission electron microscope detection and dynamic light scattering were carried out respectively. Among them, the results of transmission electron microscope detection are as follows: figure 1 Shown, the result shows, the calcium carbonate poly(lactic acid-glycolic acid) complex-DOX-NLG919 preparation that embodiment one makes is monodisperse distribution in water, shows that the calcium carbonate poly(lactic acid-glycolic acid) that the present invention makes ) compound-DOX-NLG919 preparation has a uniform particle size and is well dispersed in water.

[0043] The results of dynamic light scattering were as follows: figure 2 As shown, the results show that the calcium carbonate poly(lactic acid-...

Embodiment 3

[0044] Example 3: Detection of drug loading capacity of calcium carbonate poly(lactic acid-glycolic acid) complex preparation

[0045] The calcium carbonate poly(lactic acid-glycolic acid) complex-DOX-NLG919 preparation was qualitatively tested to detect its ability to entrap small molecule drugs. Attempt to use calcium carbonate poly(lactic acid-glycolic acid) complex preparations to entrap doxorubicin (DOX), chlorin e6 (Ce6), mitoxantrone (Mitoxantrone), bovine serum albumin (BSA) and other drugs, The method is the same as that of Example 1, except that, in the aqueous phase of emulsion B, DOX is replaced by equimolar Ce6, Mitoxantrone or BSA respectively. At the same time, PLGA-PEG nanoparticles are used as a comparison, which are mixed nanoparticles of PLGA and PLGA-PEG. The drug content in the prepared calcium carbonate poly(lactic acid-glycolic acid) complex preparation was measured by UV-VIS to test the loading capacity of the calcium carbonate poly(lactic acid-glycoli...

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Abstract

The present invention relates to a calcium carbonate poly(lactic acid-glycolic acid) composite particle and a preparation and an application thereof. The calcium carbonate poly(lactic acid-glycolic acid) composite particle is prepared by using alkyl-modified NLG919, polylactic acid-glycolic acid and polylactic acid-glycolic acid-polyethylene glycol as a shell layer, and calcium carbonate and doxorubicin as a core layer. The present invention also discloses the application of the calcium carbonate poly(lactic acid-glycolic acid) composite particle in preparation of drugs for tumor chemotherapyor combined tumor chemotherapy and immune therapy. The composite particle can be used as a drug carrier, has good drug loading efficiency and tumor enrichment ability, realizes co-loading of a chemotherapy drug DOX and an IDO inhibitor aNLG919, can also effectively release the chemotherapy drug doxorubicin and also inhibit IDO immunosuppressive pathways, effectively reverses tumor immunosuppressive microenvironment, activates tumor immunity, inhibits tumor growth, and realizes tumor chemotherapy or combined chemotherapy and immune therapy.

Description

technical field [0001] The invention relates to the field of tumor treatment preparations, in particular to calcium carbonate poly(lactic acid-glycolic acid) composite particles and its preparation and application. Background technique [0002] Tumor refers to a local mass formed by the abnormal proliferation of cells in local tissues under the action of various tumorigenic factors. Malignant tumors are what people call cancer. Chemotherapy remains the mainstay of treatment for various cancers. It is generally believed that chemotherapy works through its own cytotoxic effects. But more and more evidence shows that some specific chemotherapeutic drugs can not only kill tumor cells through cytotoxicity, but also the immune response induced by them plays an important role in the overall antitumor activity. Recent studies have shown that the antitumor chemotherapeutic drug doxorubicin (DOX) can induce immunogenic cell death (ICD) through damage-associated molecular patterns (...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/16A61K31/4188A61K31/704A61K47/02A61K47/34A61P35/00
CPCA61K9/167A61K9/1611A61K9/1647A61K31/704A61K31/4188A61P35/00A61K2300/00
Inventor 刘庄冯良珠杨志娟郝钰朱宇杰
Owner SUZHOU UNIV
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